Project Summary The proposed pilot study application, entitled Impact of Traumatic Brain Injury on Brain Aging and Dementia seeks to determine whether history of traumatic brain injury (TBI) increases risk for later life neurodegenerative decline in the Framingham Heart Study Generation 1 (Gen 1; n=5209) cohort. This project leverages available health, lifestyle, biomarker, genetic, cognitive and neuroimaging data to study TBI and its consequences in a comprehensively characterized community-based sample that has been followed prospectively for dementia for nearly 40 years. For this pilot project, we plan to identify moderate to severe TBI that is validated by medical records (vTBI) and document the prevalence of vTBI. We will then determine whether history of vTBI is associated with increased risk for accelerated cognitive decline and dementia, particularly Alzheimer's Disease. We will also examine whether the TBI metrics are associated with greater brain atrophy and changes in white matter. Further, we will address the question of whether history of vTBI is associated with short- and long-term changes in mood and daily functioning. Finally, we will also seek to identify metabolic and inflammatory biomarkers associated with vTBI and whether specific genetic markers modify the relationships between TBI and health outcomes. The results from this pilot study will lay the foundation for a larger scale study. The primary long-term objective is to determine whether the consequences of TBI are related to increased risk for dementia and other health related outcomes within a community-based sample. Results from this research will help determine the significant long- term public health implications of TBI.